Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

Chiara Bellocchi, Álvaro Fernández-Ochoa, Gaia Montanelli, Barbara Vigone, Alessandro Santaniello, Rosa Quirantes-Piné, Isabel Borrás-Linares, Maria Gerosa, Carolina Artusi, Roberta Gualtierotti, Antonio Segura-Carrettero, Marta E Alarcón-Riquelme, Lorenzo Beretta

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Abstract

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren's syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

Original languageEnglish
Article numberE1291
JournalJournal of Clinical Medicine
Volume8
Issue number9
DOIs
Publication statusPublished - Aug 23 2019

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Bellocchi, C., Fernández-Ochoa, Á., Montanelli, G., Vigone, B., Santaniello, A., Quirantes-Piné, R., Borrás-Linares, I., Gerosa, M., Artusi, C., Gualtierotti, R., Segura-Carrettero, A., Alarcón-Riquelme, M. E., & Beretta, L. (2019). Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases. Journal of Clinical Medicine, 8(9), [E1291]. https://doi.org/10.3390/jcm8091291